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Semiconductors, such as metal oxides and metal sulfides (MSX), are widely investigated as effectively catalytic materials to convert carbon dioxide (CO2) and water into chemicals under simulated solar light. These valuable investigations might address both the energy crisis and climate change in our modern society. Herein, a novel strategy to construct leaf-like heterojunctions of VS-ZnIn2S4/TiN-x is reported. The new semiconductor heterojunctions were then applied to photoelectrocatalytic CO2 reduction, achieving excellent performance (formate formation rate of 1173.2 µM h-1 cm-2) attributed to the plant cell-like morphology and enhanced electron mobility from the heterojunction interfaces to the active sites on the surface. Our findings suggest that titanium nitride (TiN) with good conductivity can improve the photoelectrocatalytic ability of MSX through heterojunction construction. The photocathode VS-ZnIn2S4/TiN-3 exhibits 81.0 % selectivity toward C2 products by optimizing the material structure and reaction conditions. According to the systematic investigation of operando Fourier transform infrared (FTIR) spectra, common intermediates such as *COO-, *COOH, *CO, *CHO, *COCHO, and *COCH3 reported in the literature were carefully verified. Among these, the carbene specie serve as the key intermediate responsible for generating other intermediates and resulting in all products.

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Plant seedling morphogenesis is considerably related to photosynthesis, pigment synthesis, and circadian periodicity during seedling development. We identified and cloned a maize zebra or crossbanding leaves mutant wk3735, which produces pale white kernels and was identified and plays a role in the equilibrium of the Redox state the in/out of ETC by active oxygen scavenging. Interestingly, it produces the zebra leaves during the production of the first seven leaves, which is apparently different from the mutation of homologs AtPTOX in Arabidopsis. It is intriguing to investigate how and why yellow crossbands (zebra leaf phenotype) emerge on leaves. As expected, chlorophyll concentration and photosynthetic efficiency both significantly declined in the yellow sector of wk3735 leaves. Meanwhile, we observed the circadian expression pattern of ZmPTOX1, which was further validated by protein interaction assays of the circadian clock protein TIM1 and ZmPTOX1. The transcriptome data of yellow (muW) and green (muG) sectors of knock-out lines and normal leaves of overexpression lines (OE) at the 5th-leaf seedling stage were analyzed. Zebra leaf etiolated sections exhibit a marked defect in the expression of genes involved in the circadian rhythm and rhythmic stress (light and cold stress) responses than green sections. According to the analysis of co-DEGs of muW vs. OE and muG vs. OE, terms linked to cell repair function were upregulated while those linked to environmental adaptability and stress response were downregulated due to the mutation of ZmPTOX1. Further gene expression level analyses of reactive oxygen species (ROS) scavenging enzymes and detection of ROS deposition indicated that ZmPTOX1 played an essential role in plant stress resistance and ROS homeostasis. The pleiotropic roles of ZmPTOX1 in plant ROS homeostasis maintenance, stress response, and circadian rhythm character may collectively explain the phenotype of zebra leaves during wk3735 seedling development.

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INTRODUCTION: Iparomlimab (QL1604) is a humanized immunoglobulin G4 mAb against programmed cell death protein 1 (PD-1). Here, we report the preliminary efficacy, safety, pharmacokinetics, and immunogenicity of iparomlimab in patients with advanced solid tumors. METHODS: In this open-label, phase 1c study, patients with advanced or metastatic solid tumors, either failed or had no standard therapies available, were enrolled and received intravenous iparomlimab at 3 mg/kg once every 3 weeks. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Between July 20, 2020, and September 6, 2021, 71 patients were enrolled and received at least one dose of iparomlimab. The ORR was 9.9% (7/71) and disease control rate was 36.6% (26/71). Median duration of response of all responders was 10.7 months [95% confidence interval (CI), 1.4-not estimable]. Additionally, the median time to progression, progression-free survival, and overall survival were 1.4 months (95% CI, 1.4-2.8), 1.4 months (95% CI, 1.4-2.7), and 9.7 months (95% CI, 7.2-15.3), respectively. A total of 52 (73.2%) patients experienced treatment-related adverse events (TRAEs) (grade ≥ 3, 19.7%). The most common TRAE (≥ 10%) was anemia (18.3%). A total of 20 (28.2%) experienced immune-related adverse events (grade ≥ 3, 7.0%). TRAEs leading to discontinuation of study drug occurred in 4 (5.6%) patients, including immune-mediated myocarditis (2 patients), Guillain-Barré syndrome (1 patient), and diarrhea (1 patient). CONCLUSIONS: Iparomlimab showed preliminary clinical activity and had a manageable safety profile in patients with advanced solid tumors. These results support further investigation of iparomlimab as monotherapy or in combination therapy in advanced solid tumors. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05801094. Retrospectively registered in 2023-03-24.

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The prosperity of the nighttime economy is an important criterion for measuring urban development. Based on regression analysis of data from 330 prefecture-level cities in China, this study explores the potential link between urban lighting and urban innovation capacity. The results show that the relationship between nighttime light intensity and urban innovation capacity follows an inverted U-shaped curve. Moreover, urban nighttime light stability moderates the above relationship. In addition, the heterogeneity analysis indicates that low population density, weak economic foundation, and high administrative grade weaken the relationship between lighting intensity and urban innovation capacity. Finally, the mechanism analysis suggested that the inverted U-shaped relationship between urban lighting and innovation capacity may be caused by the encroachment of the service industry and the loss of urban attractiveness. By exploring the proxy effect of nighttime lighting on urban innovation, this study reveals the imbalance between extrinsic image and the intrinsic capacity of cities, which not only extends the research on urban construction and development but also provides guidance for local governments concerning how to achieve all-round coordination of cities.

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Bacterial membrane vesicles (BMVs) are crucial biological vehicles for facilitating interspecies and interkingdom interactions. However, the extent and mechanisms of BMV involvement in bacterial-algal communication remain elusive. This study provides evidence of BMVs delivering cargos to targeted microalgae. Membrane vesicles (MVs) from Chitinimonas prasina LY03 demonstrated an algicidal profile similar to strain LY03. Further investigation revealed Tambjamine LY2, an effective algicidal compound, selectively packaged into LY03-MVs. Microscopic imaging demonstrated efficient delivery of Tambjamine LY2 to microalgae Heterosigma akashiwo and Thalassiosira pseudonana through membrane fusion. In addition, the study demonstrated the versatile cargo delivery capabilities of BMVs to algae, including the transfer of MV-carried nucleic acids into algal cells and the revival of growth in iron-depleted microalgae by MVs. Collectively, our findings reveal a previously unknown mechanism by which algicidal bacteria store hydrophobic algicidal compounds in MVs to trigger target microalgae death and highlight BMV potency in understanding and engineering bacterial-algae cross-talk.

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The generic self-correction method for nonlinearity-induced phase error (GSCN) can effectively suppress nonlinear error. However, GSCN directly ignores the periodic error of the 2N multiplication frequency in the error analysis stage, which still leads to errors in the suppressed results. In this paper, we propose a new method named improved generic self-correction method for nonlinearity-induced phase error in three-step phase-shifting profilometry. We retain the periodic error of the 2N multiplication frequency in the error analysis stage. In addition, based on the error model, we directly use the original fringes to compute the wrapped phases with -π/6, π/6, and π/3 phase shifts, respectively. Then, we use the original wrapped phase as the target phase and shifted the other three groups of wrapped phases to the target phase. Finally, we unwrap and fuse the four sets of wrapped phases to obtain the final corrected phase. Based on experimental results, the proposed method yields excellent reconstruction results and effectively suppresses nonlinear errors, making it highly efficient and precise.

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Epithelial-mesenchymal transition (EMT) is a complex process that plays a critical role in tumor progression. In this study, we present an EMT sensing panel for the classification of cancer cells at different EMT stages. This sensing panel consists of three types of fluorescent probes based on boronic acid-functionalized carbon-nitride nanosheet (BCN) derivatives. The selective response toward different EMT-associated biomarkers, namely, EpCAM, N-cadherin, and sialic acid (SA), was achieved by conjugating the corresponding antibodies to each BCN derivative, whereas the rare-earth-doping ensures simultaneous sensing of the three biomarkers with fluorescent emission of the three probes at different wavelengths. Sensitive sensing of the three biomarkers was achieved at the protein level with LODs reaching 1.35 ng mL-1 for EpCAM, 1.62 ng mL-1 for N-cadherin, and 1.54 ng mL-1 for SA. The selective response of these biomarkers on the cell surface also facilitated sensitive detection of MCF-7 cells and MDA-MB-231 cells with LODs of 2 cells/mL and 2 cells/mL, respectively. Based on the simultaneous sensing of the three biomarkers on cancer cells that underwent different extents of EMT, precise discrimination and classification of cells at various EMT stages were also achieved with an accuracy of 93.3%. This EMT sensing panel provided a versatile tool for monitoring the EMT evolution process and has the potential to be used for the evaluation of the EMT-targeting therapy and metastasis prediction.

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Tumor cell-derived extracellular vesicles (TEVs) contain numerous cellular molecules and are considered potential biomarkers for non-invasive liquid biopsy. However, due to the low abundance of TEVs secreted by tumor cells and their phenotypic heterogeneity, there is a lack of sensitive and specific methods to quantify TEVs. Here, we developed a dual-aptamer proximity ligation-coupled hybridization chain reaction (HCR) method for tracing TEVs, exploiting CRISPR to achieve highly sensitive detection. Taking advantage of the high binding affinity of aptamers, the two aptamers (AptEpCAM, AptHER2) exhibited the high selectivity for TEVs recognition. HCR generated long-repeated sequence containing multiple crRNA targetable barcodes, and the signals were further amplified by CRISPR upon recognizing the HCR sequences, thereby enhancing the sensitivity. Under optimal conditions, the developed method demonstrated a favorable linear relationship in the range of 2 × 103-107 particles/µL, with a limit of detection (LOD) of 3.3 × 102 particles/µL. We directly applied our assay to clinical plasma analysis, achieving 100 % accuracy in cancer diagnosis, thus demonstrating the potential clinical applications of TEVs. Due to its simplicity and rapidity, excellent sensitivity and specificity, this method has broad applications in clinical medicine.

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The aim of this study was to evaluate the cutoff value for identifying malignance in main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) with an MPD diameter ranging from 5 to 10 mm. Clinical-radiological characteristics of 142 patients, including MPD-involved IPMNs (n = 53) and branch-duct (BD)-IPMNs (n = 89) were analyzed. Logistic regression analysis was used to determine the risk factors of malignant IPMNs and invasive carcinoma. ROC curves were used to identify different cutoffs in terms of preoperative MPD values to predict the presence of invasive carcinoma as well as malignant IPMNs, and the prediction performance was evaluated. For MPD-involved IPMNs (5 mm < MPD < 10 mm), MPD diameter of 7.5 mm for discriminating malignant IPMNs (area under curve [AUC] = 0.67) and 7.7 mm for discriminating invasive IPMNs (AUC = 0.56) were found to be the optimal cutoff values at receiver operating characteristic curve (ROC) analysis. MPD > 7.5 mm and carbohydrate antigen19-9 (Ca19-9) > 37 U/ml were found to be predictors of malignant IPMNs at univariate, and MPD > 7.5 mm was a predictor in multivariate analysis in MPD-involved IPMNs. The AUC of the ROC curve of MPD (7.5 mm) combined with Ca19-9 in identifying malignant IPMNs was 0.73 in MPD-involved IPMNs. MPD (7.5 mm) combined with Ca19-9 performed well in identifying malignant IPMNs in MPD-involved IPMNs.

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Cascade reservoirs construction can greatly alter flow regime and sediment transport of rivers, further affecting migration and transformation processes of biogenic elements. The Jinsha River (JSR) is the China's largest hydropower base and the main runoff, sediment suspension, and nutrient source areas of the Yangtze River. However, the distribution, transport, and retention patterns of biogenic elements in the JSR are still unclear under the influence of cascade reservoirs. Therefore, monthly concentration monitoring work was conducted from November 2021 to October 2023 for various forms of carbon (C), nitrogen (N), phosphorus (P), and silicon (Si). Results showed that the concentrations and fluxes of total phosphorus (TP) and particulate phosphorus (PP) exhibited continuous decreasing trends along the reservoirs cascade, whereas N exhibited contrasting trends. The concentrations of dissolved total carbon (DTC), dissolved inorganic carbon (DIC), and total silicon also showed decreasing trends from upstream to downstream, whereas their fluxes were primarily influenced by runoff and exhibited upward fluctuations. Compared with other biogenic elements, there was a more pronounced retention effect on TP and PP by reservoirs, with average retention rates of 8.29 % and 16.01 %, respectively. Longer hydraulic retention time (HRT) can retain more TP and PP. Meanwhile, the retention rates of DTC, DIC, and particulate silicon were positively correlated with HRT, while the retention rate of dissolved silicon (DSi) showed a positive correlation with reservoir age. Moreover, the higher ratios of dissolved inorganic nitrogen to dissolved inorganic phosphorus (DIP) and DSi to DIP have occurred, resulting in apparent P limitation, particularly during the non-flood season due to lower DIP concentration. Overall, cascade reservoirs construction exists great influences on the spatial allocation, fluxes transport, and biogeochemical cycles of biogenic elements, potentially affecting the stability of rivers ecosystem along the food chain network.

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BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.

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Amino acids are among the most commercially promising additive solutions for achieving stable zinc anodes. However, greater attention should be given to the limitation arising from the protonation effects induced by high isoelectric point amino acids in the weakly acidic electrolytes of aqueous zinc-ion batteries (AZIBs). In this study, we introduce histidine (HIS) and ethylenediaminetetraacetic acid (EDTA) as hybrid additives into the aqueous electrolyte. Protonated HIS is adsorbed onto the anode interface, inducing uniform deposition and excluding H2O from the inner Helmholtz plane (IHP). Furthermore, the addition of EDTA compensates for the limitation of protonated HIS in excluding solvated H2O. EDTA reconstructs the solvation structure of Zn2+, resulting in a denser zinc deposition morphology. The results demonstrate that the Zn||Zn battery achieved a cycling lifespan exceeding 1480 h at 5 mA cm-2 and 5 mAh cm-2. It also reached over 900 h of cycling at a zinc utilization rate of 70 %. This study provides an innovative perspective for advancing the further development of AZIBs.

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CONTEXT: Ammonium perchlorate (NH4ClO4, abbreviated as AP) has the advantages of high oxygen content, high density, and good compatibility, and has significant application prospects in the field of energetic materials. The crystal morphology has a great influence on the properties and sensibility of energetic materials, and a single experimental means is difficult in exploring the crystals; therefore, the crystal morphology of AP is investigated using molecular dynamics simulation complemented with experiments, to theoretically analyze the differences in AP crystal habit and the interactions between solvent molecules and the main growing crystal surfaces of AP. The results show that AP crystal is mainly composed of five independent crystal surfaces (0 0 1), (0 1 0), (1 0 0), (1 0 1), and (1 0 -1) in vacuum using the BFDH laws, with (0 0 1) surface being the main growth crystal surface. In contrast, in H2O solvent, the (1 0 1) and (1 0 -1) surfaces disappear, and the AP mainly consists of (0 0 1), (0 1 0), and (1 0 0) surfaces with a rectangular shape. The crystal morphology obtained from theoretical prediction is in good agreement with that obtained from experimental culture. This paper can provide a new idea for the cultivation and preparation of AP large crystals, and promote the application of AP crystals in energetic materials. METHODS: The crystal morphologies of AP in vacuum and H2O solvent under Dreiding force field were predicted based on attachment energy model by using molecular dynamics method in Materials Studio 2019 software. The entire molecular dynamics simulation was carried out under the NTV system, the temperature control method was selected as Anderson, and the system temperature was set to 298 K. The simulation time was set to 40 ps, the step size was set to 1 fs, and the data were outputted every 5000 steps.

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BACKGROUND: Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. METHODS: We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. RESULTS: Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. CONCLUSIONS: Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

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Gastric cancer is a prevalent malignant tumor worldwide, posing challenges due to its poor prognosis and limited treatment options. Cancer stem cells (CSCs) were demonstrated as a subset of cancer cells responsible for tumor initiation and progression, and their inherent resistance to conventional chemotherapy and radiotherapy critically contributes to tumor recurrence and metastasis. Promoting the eradication of cancer stem cells is crucial for enhancing the efficacy of cancer treatments. This study introduces a novel therapeutic strategy utilizing polyhedral magnetic nanoparticles (PMNPs) functionalized with CD44 antibodies and cell-penetrating peptides (CPPs) to improve uptake by gastric cancer stem cells (MCSCs). PMNPs, synthesized via thermal decomposition, exhibited a diameter of 90 nm ± 9 nm and a saturation magnetization of 79.9 emu/g. Functionalization enhanced their uptake capabilities. Under a rotating magnetic field (RMF) of 15 Hz, PMNPs disrupted cellular structure, leading to apoptosis and ferroptosis in MCSCs. The in vitro studies showed significant reduction in MCSCs viability, while in vivo studies demonstrated tumor growth suppression with minimal side effects and high biocompatibility. This work presents a novel strategy for designing magnetic nanoparticles to mechanically destroy cancer stem cells, offering a more efficient and safety treatment option for gastric cancer.

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In this study, a UPLC-MS/MS method was developed for the rapid detection of 71 neuropsychotropic drugs in human serum for drug concentration monitoring and toxicity screening. The analytes were separated from the biological matrix by protein precipitation using a methanol-acetonitrile solvent mixture. The chromatographic separation was performed on a Kromasil ClassicShell C18 column (2.1*50 mm, 2.5 µ m) with gradient elution using acetonitrile-0.2 % acetic acid and 10 mM ammonium acetate as the mobile phases (flow rate 0.4 mL/min, column temperature 40 °C, injection volume 5 µL). An electrospray ion source in both positive and negative ion modes with multiple ion monitoring was used. The total run time was 6 min. All compounds were quantified using the isotope internal standard method. Totally, 71 drugs were detected within their linear ranges with correlation coefficients greater than 0.990. The intra- and inter-batch precision relative standard deviations (RSDs) for the low, medium, and high concentration points were less than 15 %, with an accuracy of 90%-110 %. All compounds except Moclobemide N-oxindole are stabilised within 7 days. The relative matrix effect results for each analyte were within ±20 % of the requirements. The method is validated according to Clinical and Laboratory Standards Institute guidelines, easy to use, and has a low cost.

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BACKGROUND: Stroke often results in significant respiratory dysfunction in patients. Respiratory muscle training (RMT) has been proposed as a rehabilitative intervention to address these challenges, but its effectiveness compared to routine training remains debated. This systematic review and meta-analysis aim to evaluate the effects of RMT on exercise tolerance, muscle strength, and pulmonary function in post-stroke patients. AIM: To systematically assess the efficacy of RMT in improving exercise tolerance, respiratory muscle strength, and pulmonary function in patients recovering from a stroke, and to evaluate whether RMT offers a significant advantage over routine training modalities in enhancing these critical health outcomes in the post-stroke population. METHODS: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted on October 19, 2023, without temporal restrictions. Studies were selected based on the predefined inclusion and exclusion criteria focusing on various forms of RMT, control groups, and outcome measures [including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and 6-min walking test (6MWT)]. Only randomized controlled trials (RCTs) were included. Data extraction and quality assessment were conducted independently by two reviewers using the Cochrane Collaboration's risk of bias tool. Statistical analyses, including those using the fixed-effect and random-effects models, sensitivity analysis, and publication bias assessment, were performed using Review Manager software. RESULTS: A total of 15 RCTs were included. Results indicated significant improvements in MIP (12.51 cmH2O increase), MEP (6.24 cmH2O increase), and various pulmonary function parameters (including FEV1, FVC, MVV, and PEF). A substantial increase in 6MWT distance (22.26 meters) was also noted. However, the heterogeneity among studies was variable, and no significant publication bias was detected. CONCLUSION: RMT significantly enhances walking ability, respiratory muscle strength (MIP and MEP), and key pulmonary function parameters (FEV1, FVC, MVV, and PEF) in post-stroke patients. These findings support the incorporation of RMT into post-stroke rehabilitative protocols.

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BACKGROUND: Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. METHODS: We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. RESULTS: This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. CONCLUSION: This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.

Researchers have created a comprehensive map that identifies and analyses a wide array of risk factors linked to the development of high blood pressure, using extensive data from the UK Biobank. The study revealed 964 significant factors related to lifestyle, environment, and genetics that could influence the risk of developing hypertension, with 462 of these factors showing strong evidence of a link.Key lifestyle-related findings include the impact of behaviors such as television watching and walking pace on hypertension risk, suggesting that modifiable habits can be targeted for prevention strategies.